Recurrent Tonsillitis
Conditions
Brief summary
This prospective, multicenter, randomized, double-blind, placebo-controlled, cross-over clinical trial will evaluate the efficacy and safety of Streptococcus salivarius Evol12® (Bactoblis® Evol) in reducing the recurrence and duration of acute febrile adenotonsillitis in children aged 3 to 11 years. Participants will receive either the probiotic or a matching placebo for 3 months, followed by a 7-day wash-out and a second 3-month treatment period with the alternative product. The study will assess changes in the incidence and duration of adenotonsillar episodes, antibiotic use, school absences, and sleep quality.
Detailed description
Recurrent adenotonsillitis in children is a frequent and burdensome condition, often leading to repeated antibiotic use, missed school days, and sleep disturbances. Streptococcus salivarius is a naturally occurring commensal bacterium of the oral microbiota with demonstrated ability to inhibit Streptococcus pyogenes and other pathogens responsible for pharyngotonsillitis. Streptococcus salivarius Evol12® is a novel probiotic strain with a safe microbiological profile and no antibiotic resistance, developed to restore oral microbial balance and reduce recurrent infections of the upper airways. This non-profit, prospective, multicenter, randomized, double-blind, placebo-controlled, cross-over study will enroll 216 pediatric participants aged 3 to 11 years with a history of at least three documented episodes of acute febrile adenotonsillitis in the preceding 12 months. Participants will be randomized to receive either one orodispersible tablet of S. salivarius Evol12® (Bactoblis® Evol, PharmExtracta S.p.A., Italy) daily in the evening for 3 months followed by placebo for 3 months, or vice versa, with a 7-day wash-out period between treatments. The primary objective is to evaluate the efficacy of S. salivarius Evol12® in reducing the duration and recurrence of acute febrile adenotonsillitis, as measured by the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K). Secondary objectives include assessment of sleep disorders (OSA-18 questionnaire), number and duration of feverish episodes, school days missed, antibiotic use, and symptom severity (e.g., sore throat, tonsil exudate, difficulty swallowing, otitis, cough, and fatigue). Ethical approval has been granted by the Ethics Committee of the University of Urbino Carlo Bo (Minutes No. 96, July 24, 2025).
Interventions
DIETARY_SUPPLEMENTBactoblis® Evol (Streptococcus salivarius Evol12®)
Bactoblis® Evol is an orodispersible tablet containing the probiotic strain Streptococcus salivarius Evol12® (LMG P-33696), used to support the balance of the oral microbiota. Each tablet is taken once daily in the evening, allowing it to dissolve slowly in the mouth without chewing, eating, or drinking afterward. Treatment is administered for 3 consecutive months during each treatment period. The product is manufactured by PharmExtracta S.p.A., Pontenure, Italy.
OTHERPlacebo
Matching placebo orodispersible tablet identical in appearance, flavor, and packaging to Bactoblis® Evol but without the active probiotic strain. Administered once daily in the evening for 3 months during the assigned treatment period.
Sponsors
Liaquat University of Medical & Health Sciences
University of Urbino "Carlo Bo"
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
PREVENTION
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Double-blind design: participants, caregivers, investigators, and outcome assessors are blinded to treatment allocation. The probiotic and placebo tablets are identical in appearance, packaging, and labeling.
Intervention model description
Participants will be randomized in a 1:1 ratio to receive either Streptococcus salivarius Evol12® (Bactoblis® Evol) for 3 months followed by placebo for 3 months, or the reverse sequence, with a 7-day wash-out period between treatment phases.
Eligibility
Sex/Gender
ALL
Age
3 Years to 11 Years
Healthy volunteers
No
Inclusion criteria
* Male and female children aged 3 to 11 years. * History of ≥3 documented episodes of acute adenotonsillitis within the previous 12 months, each characterized by fever ≥38°C. * Signed and accepted informed consent from a parent or legal guardian.
Exclusion criteria
* Total obstruction of the nasal cavities. * Uncontrolled gastroesophageal reflux disease. * Unilateral tonsillar enlargement. * Previous tonsil reduction surgery. * Lack of parental or legal guardian consent to participate in the study.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Reduction in recurrence of acute febrile adenotonsillitis | 6 months | Number of febrile adenotonsillitis episodes occurring during the 6-month study period. Outcomes will be assessed using the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K), completed during each febrile episode to record symptom severity and quality of life. |
| Reduction in duration of acute febrile adenotonsillitis episodes | 6 months | Duration (in days) of each febrile adenotonsillitis episode during the 6-month study period, assessed using the Wisconsin Upper Respiratory Symptom Survey for Kids (WURSS-K) completed by caregivers during illness episodes. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Occurrence of adenotonsillar symptoms | 6 months | Number of adenotonsillar symptom episodes (fever ≥38°C, sore throat, tonsil exudate, difficulty swallowing, earache, acute otitis media, fatigue or joint pain, swollen lymph nodes, or cough) reported by parents or guardians using an episode symptom card. |
| Duration of adenotonsillar symptoms | 6 months | Total duration (in days) of adenotonsillar symptom episodes (fever ≥38°C, sore throat, tonsil exudate, difficulty swallowing, earache, acute otitis media, fatigue or joint pain, swollen lymph nodes, or cough) reported by parents or guardians using an episode symptom card. |
| Change in sleep-related quality of life assessed by the Obstructive Sleep Apnea-18 (OSA-18) questionnaire | 6 months | Assessment of changes in sleep-related quality of life using the Obstructive Sleep Apnea-18 (OSA-18) questionnaire completed by the parent or legal guardian. The OSA-18 total score ranges from 18 to 126, with higher scores indicating a worse sleep-related quality of life. The questionnaire evaluates symptoms and impact across five domains: sleep disturbance, physical suffering, emotional distress, daytime problems, and caregiver concerns. |
| Number of school days missed | 6 months | Total number of school days missed due to adenotonsillar infections during the study period, as recorded in the daily symptom card. |
| Number of antibiotic treatments prescribed for adenotonsillar infections | 6 months | otal number of antibiotic treatment courses prescribed for adenotonsillar infections during the 6-month study period, as reported by parents or legal guardians on the episode symptom card. |
| Duration of antibiotic treatment for adenotonsillar infections | 6 months | Total duration (in days) of antibiotic treatment courses prescribed for adenotonsillar infections during the 6-month study period, as reported by parents or legal guardians on the episode symptom card. |
Countries
Italy
Outcome results
None listed